Key Takeaways

  • Both 0.5-mg and 0.8-mg doses of remigromig met the primary endpoint of noninferiority to ranibizumab for mean BCVA change at 52 weeks in the phase 2b/3 BRUNELLO trial
  • Higher rates of PDR, vitreous hemorrhage, and treatment discontinuations due to adverse events occurred with remigromig compared with ranibizumab, and Merck is conducting additional analyses
  • Detailed 1-year BRUNELLO data are scheduled for presentation at the AAO Annual Meeting on October 10, with remigromig continuing in additional clinical studies for retinal vascular diseases

Merck announced topline results from the pivotal phase 2b/3 BRUNELLO trial showing that both evaluated doses of remigromig met the study's primary endpoint of noninferiority to ranibizumab for visual acuity gains in adults with diabetic macular edema (DME).

At 52 weeks, remigromig 0.5 mg and 0.8 mg each demonstrated noninferiority to ranibizumab 0.5 mg for mean change from baseline in best-corrected visual acuity (BCVA), according to the company. The randomized trial enrolled 984 participants.

The safety findings, however, included imbalances that Merck said require further analysis. Although both remigromig doses were generally well tolerated, higher rates of proliferative diabetic retinopathy (PDR), vitreous hemorrhage, and treatment discontinuations due to adverse events were observed in the remigromig groups compared with ranibizumab. The company said analyses are underway to further characterize those findings.

Detailed 1-year results from BRUNELLO are scheduled for presentation at the American Academy of Ophthalmology Annual Meeting in New Orleans on October 10. Merck also plans to discuss the results with regulatory authorities.

Remigromig (MK-3000, formerly EYE103) is an investigational tetravalent, tri-specific antibody designed to activate the Wingless-related integration site, or Wnt, pathway. The pathway is involved in repairing and maintaining the blood-retinal barrier, giving the investigational therapy a mechanism distinct from established anti-VEGF treatments for retinal vascular disease.

“This is the first and only new mechanism of action in 20 years that has achieved phase 3 results noninferior to anti-VEGF therapy,” David Guyer, MD, founder, CEO, and president of EyeBio, a wholly owned subsidiary of Merck, said in the announcement.

The company said remigromig could potentially provide another treatment approach for patients with DME, including those whose disease does not fully respond to currently available therapies.

BRUNELLO is a randomized, double-masked pivotal phase 2b/3 study evaluating intravitreal remigromig at 0.5-mg and 0.8-mg doses against ranibizumab 0.5 mg in adults with DME.

The 984 participants were randomized 1:1:1 to one of the 2 remigromig regimens or ranibizumab. Treatment is administered every 4 weeks during the first year. During the second year, treatment frequency will shift according to a personalized treatment interval algorithm.

The primary endpoint is mean change from baseline to week 52 in BCVA in the study eye, assessed using standardized Early Treatment Diabetic Retinopathy Study testing. The topline announcement did not provide numerical BCVA changes, confidence intervals, the prespecified noninferiority margin, or detailed rates for the reported safety events. Those data will be important for interpreting the efficacy and safety profile when the complete results are presented.

BRUNELLO is the first of 2 phase 2b/3 studies evaluating remigromig in DME. The drug is also being investigated in the pivotal BAROLO study and in the phase 2 SUPER TUSCAN proof-of-concept study involving patients with neovascular age-related macular degeneration and retinal vein occlusion.

Merck is separately developing MK-8748, also known as Tiespectus or EYE201, an investigational bispecific antibody designed to activate the Tie2 pathway while inhibiting VEGF. The company is evaluating MK-8748 in the TORRONTES and MALBEC trials for neovascular age-related macular degeneration, and the SANGIOVESE and SYRAH studies for DME.

Merck said its broader ophthalmology development strategy is focused on retinal diseases involving vascular leakage and neovascularization.